The sexuality and social performance of androgen-deprived (castrated) men throughout history: implications for modern day cancer patients.
Androgen-deprivation therapy (ADT) via either surgical or chemical castration is the standard treatment for advanced prostate cancer (PCa). In North America, it is estimated that more than 40,000 men start ADT each year. The side effects of this treatment are extensive and include gynecomastia, erectile dysfunction, and reduced libido. These changes strongly challenge patients' self-identity and sexuality. The historical term for a man who has been castrated is 'eunuch', now a pejorative term implying overall social and sexual impotence. In this paper, we review key historical features of eunuch social performance and sexuality from a variety of cultures in order to assess the validity of contemporary stereotypes of the androgen-deprived male. Data were taken from secondary sources on the history of Byzantium, Roman Antiquity, Early Islamic societies, the Ottoman Empire, Chinese Dynasties, and the Italian Castrati period. This cross-cultural survey shows that castrated men consistently held powerful social positions that yielded great political influence. Many eunuchs were recognized for their loyalty, managerial style, wisdom, and pedagogical skills. Furthermore, rather than being consistently asexual and celibate, they were often sexually active. In certain cultures, they were objects of sexual desire for males, or females, or both. Collectively, the historical accounts suggest that, given the right cultural setting and individual motivation, androgen deprivation may actually enhance rather than hinder both social and sexual performance. We conclude that eunuch history contradicts the presumption that androgen deprivation necessarily leads to social and sexual impotence. The capabilities and accomplishments of eunuchs in the past gives patients on ADT grounds for viewing themselves in a positive light, where they are neither socially impotent nor sexually chaste.


A user evaluation of a local air ambulance service in North Wales.
The purpose of this paper is to examine the current state and utilisation of user evaluation consultation adopted by Wales Air Ambulance (WAA) within the policy context. It is intended to provide a baseline for further evaluative research in the field and to highlight existing practices and resources. Gaps in strategic planning and service delivery are identified, with local recommendations proposed. Semi-structured, in-depth face-to-face interviews were conducted with ten participants drawn from a convenient sample representative of stakeholders including practitioners, fundraisers and operational staff. These groups represent primary actors involved in the delivery of services and policy implementation and also secondary actors involved in the delivery as users. Documentary analysis of WAA dispatch policy and protocols combined with secondary quantitative data of key performance indicators was undertaken. In total, 80 per cent of the sample stated their satisfaction with WAA dispatch policy with no perceived need or benefit to further development of policy or local agreements. About 70 per cent of participants had received direct comments that were 100 per cent positive from primary users/patients. All organisations shared the same concerns regarding lack of appropriate present communication. The research design was driven by practicalities of time-scale and resources. Owing to these constraints, plus the legal and ethical requirements relating to the involvement of patients in research, primary users were not included in this study. Areas for future research are identified. Recommendations being implemented by WAA include further engagement with primary users of the service in order to enhance standards. This paper reports the first empirical research conducted with WAA and users of the service.


Strategies to Support Tobacco Cessation and Tobacco-Free Environments in Mental Health and Substance Abuse Facilities.
We identified and described strategies for promoting smoking cessation and smoke-free environments that were implemented in Oregon and Utah in treatment centers for mental illness and substance abuse. We reviewed final evaluation reports submitted by state tobacco control programs (TCPs) to the Centers for Disease Control and Prevention and transcripts from a call study evaluation. The TCPs described factors that assisted in implementing strategies: being ready for opportunity, having a sound infrastructure, and having a branded initiative. These strategies could be used by other programs serving high-need populations for whom evidence-based interventions are still being developed.


Cyclewise Operation of Printed MoS2 Transistor Biosensors for Rapid Biomolecule Quantification at Femtomolar Levels.
Field-effect transistors made from MoS2 and other emerging layered semiconductors have been demonstrated to be able to serve as ultrasensitive biosensors. However, such nanoelectronic sensors still suffer seriously from a series of challenges associated with the poor compatibility between electronic structures and liquid analytes. These challenges hinder the practical biosensing applications that demand rapid, low-noise, highly specific biomolecule quantification at femtomolar levels. To address such challenges, we study a cyclewise process for operating MoS2 transistor biosensors, in which a series of reagent fluids are delivered to the sensor in a time-sequenced manner and periodically set the sensor into four assay-cycle stages, including incubation, flushing, drying, and electrical measurement. Running multiple cycles of such an assay can acquire a time-dependent sensor response signal quantifying the reaction kinetics of analyte-receptor binding. This cyclewise detection approach can avoid the liquid-solution-induced electrochemical damage, screening, and nonspecific adsorption to the sensor and therefore improves the transistor sensor's durability, sensitivity, specificity, and signal-to-noise ratio. These advantages in combination with the inherent high sensitivity of MoS2 biosensors allow for rapid biomolecule quantification at femtomolar levels. We have demonstrated the cyclewise quantification of Interleukin-1β in pure and complex solutions (e.g., serum and saliva) with a detection limit of ∼1 fM and a total detection time ∼23 min. This work leverages the superior properties of layered semiconductors for biosensing applications and advances the techniques toward realizing fast real-time immunoassay for low-abundance biomolecule detection.


Role of cholecystokinin in the control of gastric emptying and secretory response to a fatty meal in normal subjects and duodenal ulcer patients.
Exogenous cholecystokinin (CCK) is known to affect gastric motor and secretory activities, but its physiologic role in the control of gastric functions is unknown. In this study involving 10 young healthy subjects and 10 duodenal ulcer (DU) patients, 500 ml of a standard meal without or with addition of 15% soybean oil was given, and the gastric emptying rate and the pH profile and plasma levels of gastrin, CCK, pancreatic polypeptide (PP), and somatostatin were determined in separate tests with placebo or with antagonism of type-A CCK receptors (loxiglumide, 1200 mg orally). In healthy controls and DU patients the emptying half-time was 44 and 34 min, respectively, and the addition of oil prolonged the emptying by about 50%. Pretreatment with loxiglumide significantly reduced fat-induced retardation of gastric emptying in both healthy controls and DU patients. A standard meal in healthy subjects resulted in an immediate rise in median gastric pH to about 6.0, and this was followed by gradual decrease within about 3 h to premeal values of about 2.0. After the meal, plasma gastrin rose by 57%, CCK by 177%, PP by 100%, and somatostatin by 39%. Addition of fat significantly attenuated and prolonged the pH decrease after the meal while reducing the increment in plasma gastrin and enhancing plasma CCK and PP levels. Loxiglumide significantly reduced the median postprandial pH (from control 4.8 to 2.5) and reversed the changes in the pH profile caused by the addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin and PP were significantly attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin in DU patients. These results indicate that endogenous CCK released by a fatty meal delays gastric emptying and inhibits gastric acid and plasma gastrin responses in healthy subjects, but in DU patients the inhibitory effect of CCK is less pronounced, suggesting a defect in the action of this hormone on gastrin release and gastric acid secretion.


Diabetes and hypertension.
Diabetes mellitus is associated with increased risk of cardiovascular morbidity and mortality which often can be attributed to the frequent coexistence of arterial hypertension. There is an additive effect of high blood pressure and elevated blood sugar on the severity, extent and rate of progression of atherosclerotic macrovascular disease. Current evidence has also linked hypertension to acceleration of the chronic microvascular complications of diabetes mellitus including diabetic nephropathy and retinopathy. These facts emerge to place diabetic hypertension as a most important public health issue. Questions of frequency, aetiology and the implications of intervention therapy for hypertension in diabetes mellitus are reviewed in this article and can be found in several recent reviews.


Microfluidic Mobility Shift Profiling of Lysine Acetyltransferases Enables Screening and Mechanistic Analysis of Cellular Acetylation Inhibitors.
Lysine acetyltransferases (KATs) are critical regulators of signaling in many diseases, including cancer. A major challenge in establishing the targetable functions of KATs in disease is a lack of well-characterized, cell-active KAT inhibitors. To confront this challenge, here we report a microfluidic mobility shift platform for the discovery and characterization of small molecule KAT inhibitors. Novel fluorescent peptide substrates were developed for four well-known KAT enzymes (p300, Crebbp, Morf, and Gcn5). Enzyme-catalyzed acetylation alters the electrophoretic mobility of these peptides in a microfluidic chip, allowing facile and direct monitoring of KAT activity. A pilot screen was used to demonstrate the utility of microfluidic mobility shift profiling to identify known and novel modulators of KAT activity. Real-time kinetic monitoring of KAT activity revealed that garcinol, a natural product KAT inhibitor used in cellular studies, exhibits time-dependent and detergent-sensitive inhibition, consistent with an aggregation-based mechanism. In contrast, the cell-permeable bisubstrate inhibitor Tat-CoA exhibited potent and time-independent KAT inhibition, highlighting its potential utility as a cellular inhibitor of KAT activity. These studies define microfluidic mobility shift profiling as a powerful platform for the discovery and characterization of small molecule inhibitors of KAT activity, and provide mechanistic insights potentially important for the application of KAT inhibitors in cellular contexts.


The connective tissue and ligaments of the distal interphalangeal joint: a review and investigation using ultra-high field 16.4 Tesla magnetic resonance imaging.
This study reviews the literature on the anatomy of the connective tissues surrounding the distal interphalangeal joint and further characterizes the three-dimensional relationships of these structures with ultra-high field magnetic resonance imaging. Ten cadaver fingers, fixed in a solution of 5% agar and 4% formalin, were imaged utilising an ultrashield 16.4 Tesla ultra-high field magnetic resonance imaging, yielding a total of 4000 images. Images were analysed using Osirix™ (version 5.5.1 32 bit edition) for three-dimensional reconstruction. We found numerous conflicting descriptions of the connective tissue structures around the distal interphalangeal joint. Based upon our literature review and imaging studies we have defined precisely Cleland's ligaments, the oblique proximal septum, Grayson's ligaments, the dorsal plate, and the interosseous ligaments of the distal interphalangeal joint.


Intradendritic recordings from neurons of motor cortex of cats.
The properties of neuronal spike potentials ranging from 20 to 60 mV in size were studied in stable recordings made from the motor cortex of unanesthetized, unparalyzed cats. Histologic evidence that injection of horseradish peroxidase (HRP) was confined to single neurons and appropriately high levels of potassium measured with K+ ion-sensitive electrodes indicated that these recordings were obtained from single, intracellularly penetrated neurons. Pressure injection of small volumes of 4% HRP in 1 M KC1, intracellularly, was characteristically associated with transient increases in spike size and decreases in input resistance. Recoveries of HRP-filled dendritic processes without filling of somata were obtained from penetrations giving spikes smaller than the recorded resting potential (spike-undershoot recordings). Recordings with dendritic recoveries had higher input resistances and showed greater increases in spike size during pressure injection than did recordings with both somata and dendrites recovered. The activity in response to a weak click elicited in cells with spike potentials between 20 and 40 mV was as great or greater than that elicited in cells with larger spike potentials or in extracellularly recorded units. We conclude that many stable spike-undershoot recordings of neurons of the motor cortex of awake cats reflect penetrations of dendritic processes as opposed to injury because they show a) a normal functional response to weak auditory stimuli delivered over periods of many minutes, b) a reversible increase in spike size during pressure injection of small volumes of HRP in KC1 consistent with penetration of a cable remote from the site of spike generation, and c) the frequent recovery of HRP-marked dendrites without somata.


Effectiveness of mindfulness-based stress reduction in a community sample over 2 years.
Although numerous studies have demonstrated that mindfulness-based stress reduction (MBSR) improves clinical and nonclinical outcomes, few studies have followed MBSR participants for >12 months, and few have analyzed post-intervention home practice. We followed a community sample of 247 self-referred adults for 2 years after completion of an 8-week MBSR program. Dependent variables, including self-reported anxiety, depression, perceived wellness, mindfulness, and duration and frequency of continued home practice, were measured before and after the program and every 6 months after. Participants reported significantly improved symptoms of depression and anxiety, increased perceived wellness, and increased mindfulness after the 8-week intervention compared with preintervention reports. These improvements persisted for 2 years. Correlations between post-intervention home practice and mindfulness indicated that individuals who continued to practice developed greater mindfulness, which was associated with improved mental health and wellness. Participants who completed the MBSR program reported significant improvements in anxiety, depression, perceived wellness, and mindfulness during the program.


Regulatory supervision of sites for spent fuel and radioactive waste storage in the Russian northwest.
In the 1960s two technical bases for the Northern Fleet were created in the Russian northwest at Andreeva Bay in the Kola Peninsula and Gremikha village on the coast of the Barents Sea. They maintained nuclear submarines, receiving and storing radioactive waste and spent nuclear fuel. No further waste was received after 1985, and the technical bases have since been re-categorised as temporary storage sites. The handling of these materials to put them into a safe condition is especially hazardous because of their degraded state. This paper describes regulatory activities which have been carried out to support the supervision of radiological protection during recovery of waste and spent fuel, and to support regulatory decisions on overall site remediation. The work described includes: an assessment of the radiation situation on-site; the development of necessary additional regulatory rules and standards for radiation protection assurance for workers and the public during remediation; and the completion of an initial threat assessment to identify regulatory priorities. Detailed consideration of measures for the control of radiation exposure of workers and radiation exposure of the public during and after operations and emergency preparedness and response are complete and provided in sister papers. The continuing requirements for regulatory activities relevant to the development and implementation of on-going and future remediation activities are also outlined. The Norwegian Radiation Protection Authority supports the work, as part of the Norwegian Government's plan of action to promote improvements in radiation protection and nuclear safety in northwest Russia.


The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems.
Obesity (Ob) poses a significant risk factor for the onset of metabolic syndrome with associated complications, wherein the Mesenchymal Stem Cell (MSC) therapy shows pre-clinical success. Here, we explore the therapeutic applications of human Placental MSCs (P-MSCs) to address Ob-associated Insulin Resistance (IR) and its complications. In the present study, we show that intramuscular injection of P-MSCs homed more towards the visceral site, restored HOMA-IR and glucose homeostasis in the WNIN/GR-Ob (Ob-T2D) rats. P-MSC therapy was effective in re-establishing the dysregulated cytokines. We report that the P-MSCs activates PI3K-Akt signaling and regulates the Glut4-dependant glucose uptake and its utilization in WNIN/GR-Ob (Ob-T2D) rats compared to its control. Our data reinstates P-MSC treatment's potent application to alleviate IR and restores peripheral blood glucose clearance evidenced in stromal vascular fraction (SVF) derived from white adipose tissue (WAT) of the WNIN/GR-Ob rats. Gaining insights, we show the activation of the PI3K-Akt pathway by P-MSCs both in vivo and in vitro (palmitate primed 3T3-L1 cells) to restore the insulin sensitivity dysregulated adipocytes. Our findings suggest a potent application of P-MSCs in pre-clinical/Ob-T2D management.


Protective effect of bradykinin antagonist Hoe-140 during in vivo myocardial ischemic-reperfusion injury in the cat.
The effect of icatibant (Hoe-140), a selective bradykinin receptor (B(2)) antagonist on myocardial ischemic-reperfusion injury was studied in open chest barbiturate anaesthetized cats. The left anterior descending coronary artery was occluded for 15 min, followed by 60 min of reperfusion. Saline or icatibant (200 microg/kg) was administered intravenously slowly over 2 min, 5 min before reperfusion. In the saline-treated group, myocardial ischemic-reperfusion injury was evidenced by depressed MAP, depressed peak positive and negative dP/dt and elevated left ventricular end-diastolic pressure and enhanced oxidative stress [elevated plasma thiobarbituric acid reactive substances (TBARS; a marker for lipid peroxidation), depressed myocardial GSH (reduced glutathione), superoxide dismutase (SOD), catalase] and depletion of adenosine triphosphate (ATP) along with rise in plasma creatine phosphokinase (CPK). Administration of icatibant resulted in complete hemodynamic recovery together with repletion of ATP and reduction in plasma TBARS without any significant change in myocardial SOD, catalase and GSH. The results of the present study suggest a protective role of icatibant in myocardial ischemic-reperfusion injury.


Bidirectional chiral inversion of the enantiomers of the nonsteroidal antiinflammatory drug oxindanac in dogs.
The nonsteroidal antiinflammatory drug oxindanac exists as two enantiomers, with most of its pharmacological activity residing in the (S)-isomer. The behavior of its enantiomers was investigated in dogs. Bidirectional inversion occurred in heparinised plasma and blood, with a ratio of enantiomers [S:R] of 7.3:1 being achieved at equilibrium after incubation for 24 h at 37 degrees C. There was no detectable inversion of either isomer in plasma incubated at 4 degrees C for up to 8 h or in aqueous solution at 37 degrees C for up to 36 h. Bidirectional inversion also occurred in vivo, with a ratio of plasma AUC (0 infinity)s [S:R] of 8.1:1. The ratio of enantiomers reached equilibrium within 2 hr following (S)- or rac-oxindanac, and within 8 h following (R)-oxindanac. Elimination t1/2s of the isomers were the same (R, 12.1 h, S, 13.3 h). There were no differences in the ratio of enantiomers following oral or intravenous application, suggesting that a systemic site for inversion was predominant. Although concentrations of the respective isomers were similar at equilibrium following administration of either (R)-, (S)-, or rac-oxindanac, AUC (0 infinity)s differed due to the delay in reaching equilibrium. The extent of inversion to the (S)-isomer was 100, 73.2, and 60.7% after administration of (S)-, rac-, and (R)-oxindanac, respectively. Although pharmacological activity might be equivalent at equilibrium following administration of either (R)-, (S)-, or rac-oxindanac; efficacy at early time points should be superior in the order (S) > racemate > (R).(ABSTRACT TRUNCATED AT 250 WORDS)


Near infrared reflectance spectroscopic determination of protein nitrogen in plant tissue.
A rapid, nondestructive method is described for the determination of protein nitrogen in plant tissue, using near infrared reflectance (NIR) spectroscopy. Procedures for instrument calibration are discussed. Comparisons between Kjeldahl nitrogen and NIR nitrogen are made for corn leaf tissue from Georgia and Indiana. Multiple correlation coefficients for other plant tissues such as peanuts, soybean, wheat, pecan, bermuda grass, and bent grass are also shown.


Role of the immune response induced by superantigens in the pathogenesis of microbial infections.
Superantigens (SAgs) are microbial proteins which have potent effects on the immune system. They are presented by major histocompatibility complex (MHC) class II molecules and interact with a large number of T cells expressing specific T cell receptor V beta domains. Encounter of a SAg leads initially to the stimulation and subsequently to the clonal deletion of reactive T cells. SAgs are expressed by a wide variety of microorganisms which use them to exploit the immune system to their own advantage. Bacterial SAgs are exotoxins which are linked to several diseases in humans and animals. A classical example is the toxic shock syndrome in which the massive release of cytokines by SAg-reactive cells is thought to play a major pathogenic role. The best characterized viral SAg is encoded by mouse mammary tumour virus (MMTV) and has proved to have a major influence on the viral life cycle by dramatically increasing the efficiency of viral infection. In this paper, we review the general properties of SAgs and discuss the different types of microorganisms which produce these molecules, with a particular emphasis on the role played by the SAg-induced immune response in the course of microbial infections.


Left ventricular reverse remodeling after successful subannular mitral valve repair in end-stage heart failure: a case report.
Due to ongoing left ventricular (LV) remodeling and consecutive geometric displacement of both papillary muscles, end-stage heart failure is frequently associated with relevant functional mitral regurgitation (FMR) Type IIIb. Treatment strategies of FMR and their prognostic impact are still controversial. We present a case of an 80-year-old patient who suffered from recurrent symptoms of congestive heart failure due to dilated cardiomyopathy and concomitant severe FMR. To specifically address severe tethering of both mitral leaflets heart team decision was to perform minimally invasive mitral valve repair (MVR) including a subannular LV remodeling procedure, instead of an interventional edge-to-edge repair (MitraClip® procedure). In addition to mitral valve ring annuloplasty, standardized relocation of both papillary muscles was performed successfully, leading to a complete resolution of mitral leaflet tethering. There were no procedural complications and the patient was discharged with an excellent functional result without residual mitral regurgitation. Furthermore, after 12 and 24 months, he reported an increase of his functional exercise capacity and a remarkable reverse LV remodeling could be demonstrated. Novel subannular repair techniques, especially the relocation of both papillary muscles, specifically address severe leaflet tethering in FMR and have an obvious potential to improve long-term competence of MVR. Therefore, they could be considered as a viable therapeutic option even in elderly patients presenting with end-stage cardiomyopathy and severe leaflet tenting.


Rapid detection of Listeria monocytogenes by a PCR assay specific for an aminopeptidase.
Specific and rapid detection of Listeria monocytogenes is very important with regard to food safety since all other species of Listeria appear to be non-pathogenic to humans. Conventional microbiological detection methods are very time consuming. The polymerase chain reaction (PCR) is one of the most promising techniques for rapid detection of micro-organisms in food products. We have developed a PCR assay, specific for L. monocytogenes, based on the gene encoding an aminopeptidase, which previously has not been described for this species. The L. monocytogenes aminopeptidase shares strong sequence similarity with aminopeptidase C from Streptococcus thermophilous, Lactobacillus lactis, Lactobacillus helveticus, and with a cysteine proteinase from Saccharomyces cerevisiae. Polymerase chain reaction primers were synthesized based on the DNA sequence of the aminopeptidase gene. A 90 bp product was apparent with all L. monocytogenes strains tested but not with other species of Listeria or other bacterial genera. The PCR assay, which is performed directly from whole bacterial cells, does not involve DNA purification and can be conducted in 4 h. It provided positive identification of L. monocytogenes in mixed culture.


Micromachined piezoelectric microphones with in-plane directivity.
Micromachined piezoelectric microphones with in-plane directivity are introduced. A beam rotates about center torsional pivots and is attached to piezoelectrically active end-springs. Rotation of the beam in response to sound pressure gradients produces spring deflections, which, in turn, produce an open-circuit voltage at the piezoelectric films. Prototypes are presented that contain a 20-μm-thick silicon beam and end-springs with 900-nm-thick chemical solution deposited lead zirconate titanate atop the surface of the end-springs. Acoustic directivity measurements are presented that confirm device functionality.


Suppression of the progress of necrosis after coronary artery ligation in the dog by pharmacologic interventions.
A study was carried out of a therapy supporting the anaerobic glycolysis and coronary perfusion of ischemic myocardium and preserving its potassium and magnesium contents, which consisted in combined administration of hyaluronidase, glucose, insulin, Tris, methoxamine, and potassium and magnesium aspartate. The drugs were administered to Beagle dogs between 30 minutes and 20 hours after the ligation of the left anterior descending coronary artery. The size of infarction was determined by the Nachlas method, which is based on the detection of activities of dehydrogenases in heart slices. Treated animals showed a reduced infarction size (p less than 0.001). The evidence of the favourable effect of the therapy used was brought also by hemodynamic measurements. The heart rate was slower (p less than 0.02) and the mean arterial blood pressure was higher (p less than 0.001) in treated animals than in control ones (as evaluated at the end of the experimental period). Significant correlation between the infarction size and the heart rate on the one hand and the mean arterial pressure on the other hand was found (r = 0.59, p less than 0.01; r=--0.47, p less than 0.05, respectively).


[Multicenter evaluation of oral antibiotics: resistance behavior in 5 Swiss centers].
The susceptibility of 2196 fresh clinical isolates to twelve different oral compounds was assessed in five Swiss microbiology institutions during summer 1992. A standardized microdilution system including all other material necessary was employed to assess the antibacterial activity of penicillin G, ampicillin, ampicillin + sulbactam, amoxycillin + clavulanic acid, cefadroxil, cephalexin, cefaclor, cefuroxime, cefetamet, doxycycline, erythromycin and clindamycin. The aminopenicillins (including the beta-lactamase inhibitor combinations) were highly active against the streptococci, in combination with a beta-lactamase inhibitor they covered the majority of the bla+ E. coli and Proteus mirabilis and between 60 to 80% of the Klebsiella spp. and Proteus vulgaris isolates. All the cephalosporins exhibited good activity against the streptococci, they were active against Gram-negative fermentative rods to a varying degree. Cefetamet was also active against many cefaclor and cefuroxime-resistant isolates. A considerable part of the species studied exhibited resistance to doxycycline; the observed resistance of S. agalactia, P. mirabilis, and Morganella morganii agreed with previous findings. Most of the Streptococcus spp. were inhibited by erythromycin and clindamycin. There were only single penicillin resistant S. pneumoniae isolates in the five Swiss centers. Taking account of the above particulars the epidemiology of antimicrobial resistance in Switzerland can be considered satisfactory.


Occurrence of the (2R,3S)-Isomer of 2-Amino-3,4-dihydroxybutanoic Acid in the Mushroom Hypsizygus marmoreus.
Here, we report the occurrence of the (2R,3S)-isomer of 2-amino-3,4-dihydroxybutanoic acid (d-ADHB) in the fruiting body of an edible mushroom, Hypsizygus marmoreus. This is an unusual example of the accumulation of a d-amino acid whose enantiomer is not a proteinogenic amino acid. We show that d-ADHB occurs specifically in the mushroom H. marmoreus. Other edible mushrooms examined, including Pholiota microspora, Pleurotus eryngii, Mycena chlorophos, Sparassis crispa, Grifola frondosa, Pleurotus ostreatus, and Flammulina velutipes, do not contain detectable levels of d-ADHB. The concentration of d-ADHB in the fruiting body of H. marmoreus is relatively high (approximately 1.3 mg/g of fruiting body) and is comparable to the concentration of some of the most abundant free proteinogenic amino acids. Quantitative analysis of d-ADHB during fruiting body development demonstrated that the amino acid is synthesized during the fruiting body formation period. The absence of the putative precursors of d-ADHB, the (2S,3S)-isomer of ADHB and 2-oxo-tetronate, and the enzyme activities of d-ADHB racemase (2-epimerase) and transaminase suggested that d-ADHB is synthesized by a unique mechanism in this organism. Our data also suggested that the lack of or low expression of a d-ADHB degradation enzyme is a key determinant of d-ADHB accumulation in H. marmoreus.


Suicidal self-poisoning in childhood.
The authors present an epidemiological study of the suicide attempt in childhood committed by self-poisoning in Bulgaria. Materials and data of the Children Toxicology Department at the National Toxicology Center, EMI "Pirogov", Sofia, Bulgaria for the period 2003-2004 are used. These data are compared with data for 1973-1994 for the region of Sofia, as well as for the 1985-1994 for the region of Vidin, Bulgaria. The suicide attempts are described according to type of poisoning, type of toxic substance consecutiveness of the attempt, age group, sex, social and family status of the children, distribution by seasons, days of the week and hours of the day, grades of severity of the intoxication. The incidence of schizophrenic type of disorders and affective disorders in children with suicide attempts is comparatively low-about 2%. The main motives of the self-poisonings in childhood are problematic relationship in the family, conflict of the generations, emotional disappointments, and fear of punishment.


Prospective study on the management of trigger finger.
Trigger finger is one of the very common conditions encountered in hand surgery. Currently, the treatment modes we offer in our clinics are combination therapy of topical NSAIDS, occupational therapy and splinting or invasive modes involving corticosteroid injections and trigger finger release. This is a prospective review looking at the outcomes of the various initial treatment modules currently used for treating trigger fingers and the rate of surgery following non-surgical treatment. From our study we have noted that 26% of the digits which were subjected to combination therapy eventually underwent surgery whereas 60% of digits which received corticosteroid injections underwent surgery. Even though our results comparing operation rates are not statistically significant, they appear to show that combination therapy was more effective in avoiding surgery than corticosteroid injection in lower grades of trigger.


The impact of single and shared rooms on family-centred care in children's hospitals.
To explore whether and how spatial aspects of children's hospital wards (single and shared rooms) impact upon family-centred care. Family-centred care has been widely adopted in paediatric hospitals internationally. Recent hospital building programmes in many countries have prioritised the provision of single rooms over shared rooms. Limited attention has, however, been paid to the potential impact of spatial aspects of paediatric wards on family-centred care. Qualitative, ethnographic. Phase 1; observation within four wards of a specialist children's hospital. Phase 2; interviews with 17 children aged 5-16 years and 60 parents/carers. Sixty nursing and support staff also took part in interviews and focus group discussions. All data were subjected to thematic analysis. Two themes emerged from the data analysis: 'role expectations' and 'family-nurse interactions'. The latter theme comprised three subthemes: 'family support needs', 'monitoring children's well-being' and 'survey-assess-interact within spatial contexts'. Spatial configurations within hospital wards significantly impacted upon the relationships and interactions between children, parents and nurses, which played out differently in single and shared rooms. Increasing the provision of single rooms within wards is therefore likely to directly affect how family-centred care manifests in practice. Nurses need to be sensitive to the impact of spatial characteristics, and particularly of single and shared rooms, on families' experiences of children's hospital wards. Nurses' contribution to and experience of family-centred care can be expected to change significantly when spatial characteristics of wards change and, as is currently the vogue, hospitals maximise the provision of single rather than shared rooms.


Intraspecific variability in Phaeocystis antarctica's response to iron and light stress.
Phaeocystis antarctica is an abundant phytoplankton species in the Southern Ocean, where growth is frequently limited by iron and light. Being able to grow under low iron conditions is essential to the species' success, but there have been hints that this ability differs among clones. Here, we compare the growth, cell size and chlorophyll a concentrations of four P. antarctica clones cultured under different iron and light conditions. Iron was provided either as unchelated iron (Fe') or bound to the bacterial siderophore desferrioxamine B, representing, respectively, the most and least bioavailable forms of iron which phytoplankton encounter in the marine environment. The growth rate data demonstrate that the clones vary in their ability to grow using organically bound iron, and that this ability is not related to their ability to grow at low inorganic iron concentrations. These results are consistent at low and high light. Physiologically, only three of the four clones shrink or decrease the concentration of chlorophyll a in response to iron limitation, and only one clone decreases colony formation. Together, our data show that P. antarctica clones 1) respond to the same degree of iron limitation using different acclimation strategies, and 2) vary in their ability to grow under the same external iron and light conditions. This physiological diversity is surprisingly large for isolates of a single phytoplankton species.


Burn injury and prevention in the Lebanon War, 1982.
Measures taken during the Lebanon War, 1982, to prevent and minimize the extent and severity of tank-crew combat burns proved to be of value. Since 98% of tank crewmen who were burned were wearing fireproof suits at the time, only 12% sustained abdominal burns; 77% had facial burns, as none of them were wearing fireproof masks. Only 9% of the burned soldiers who wore fireproof gloves sustained hand burns, compared with 75% who did not wear the gloves. A comparison of the extent of tank-crew burns in the Lebanon War and the October 1973 War revealed that 51% of the burns in 1982 were minor, compared with 21% in 1973. Of the burns sustained in 1973, 29% covered greater than 40% of the body surface area, compared with 18% in 1982.


Increased levels of markers of vascular inflammation in patients with coronary heart disease.
Elevated levels of soluble cell adhesion molecules (sCAMs), inflammatory cytokines and C-reactive protein (CRP) have been associated with atherosclerotic disease states. The aim of the present study was to evaluate whether circulating levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E- and P-selectin were significantly elevated in patients with coronary heart disease (CHD) compared with healthy controls, and to study possible associations between these sCAMs, tumour necrosis factor alpha (TNFalpha). interleukin-6 (IL-6), CRP and major CHD risk factors. The study included 193 patients in various stages of CHD and 193 matched controls. To evaluate any possible influence of acute phase reaction, reinvestigation was performed after 6 months. After adjustment for major CHD risk factors, sVCAM-1, sICAM-1, P-selectin, IL-6 and CRP remained significantly elevated in the CHD patients (p for all <0.001). In multivariate analysis sVCAM-1 was predicted by age (p=0.015), sICAM-1 by smoking (p<0.001) and total cholesterol (p=0.026), E-selectin by body mass index (BMI) (p=0.004) and P-selectin by male gender (p=0.015). TNFalpha significantly predicted sICAM-1 and E-selectin levels, while IL-6 predicted CRP but none of the sCAMs measured. This might indicate that TNFalpha, but not IL-6, plays a major role in the regulation of sCAM levels in vivo.


Extracellular Vesicles in the Pathogenesis, Treatment, and Diagnosis of Spinal Cord Injury: A Mini-Review.
Benefiting from in-depth research into stem cells, extracellular vesicles (EVs), which are byproducts of cells and membrane-wrapped microvesicles (30-120 nm) containing lipids, proteins, and nucleic acids, may cast light on the research and development of therapeutics capable of improving the neurological recovery of spinal cord injury (SCI) animals. However, the mechanistic modes of action for EVs in alleviating the lesion size of SCI remain to be solved, thus presenting a tremendous gap existing in translation from the laboratory to the clinic. The purpose of this minireview was to cover a wide range of basic views on EVs involved in SCI treatment, including the effects of EVs on the pathogenesis, treatment, and diagnosis of spinal cord injury. We searched databases (i.e., PubMed, Web of Science, Scopus, Medline, and EMBASE) and acquired all accessible articles published in the English language within five years. Studies reporting laboratory applications of EVs in the treatment of SCI were included and screened to include studies presenting relevant molecular mechanisms. This review first summarized the basic role of EVs in cell communication, cell death, inflammatory cascades, scar formation, neuronal regrowth, and angiogenesis after SCI, thereby providing insights into neuroprotection and consolidated theories for future clinical application of EVs. EVs participate in an extremely wide range of cell activities, play a critical role in cell communication centring neurons, and are considered potential therapies and biomarkers for SCI. miRNAs are the most abundant nucleic acids shipped by EVs and effluent cytokines, and they may represent important messengers of EVs and important factors in SCI treatment.


Hereditary postprandial hypertriglyceridemic rabbit exhibits insulin resistance and central obesity: a novel model of metabolic syndrome.
We have established a hereditary postprandial hypertriglyceridemic (PHT) rabbit. The present study was designed to define whether this rabbit model represents both insulin resistance and central obesity. Body weight, abdominal circumference, visceral fat weight, and glucose tolerance were compared between PHT and Japanese white (JW) rabbit. Plasma levels of triglycerides (TG), total cholesterol (TC), glucose, and insulin were measured before and after feeding. Abdominal circumference of PHT rabbit was larger than that of JW rabbit, with no difference in body mass index. Visceral fat accumulation was noted as obvious in mesenterium, retroperitoneal space, and epididymal area. Plasma TG and TC levels were high preprandially and markedly increased postprandially in PHT rabbit compared with JW rabbit. Although plasma glucose levels were comparable in both groups, plasma insulin levels were elevated in PHT rabbit. Glucose tolerance tests indicated that plasma insulin levels in PHT rabbit were consistently higher than in JW rabbit. A positive correlation was observed between plasma insulin levels and visceral fat weight in PHT rabbit. PHT rabbit shows insulin resistance along with central obesity. PHT rabbit will serve as a model for elucidating genetic predisposition and pathophysiology in metabolic syndrome.


Cooling effect of fungal stromata in the Dactylis-Epichloë-Botanophila symbiosis.
The stromata of Epichloë fungi are structures covering part of the stem of grasses. Under the fungal layer, still green tissues of the plant survive, although the development of the new leaves is inhibited. Stromata are the places where conidia and ascospores develop. Also, here Botanophila flies dine on mycelium, lay the eggs, defecate, and the larvae develop. The interaction of the three symbionts was analyzed concerning the organisms' adaptation to understand the differences in physiology and ecology of this microenvironment that support stable symbiosis spreading presently in Europe since the beginning of the XXI century. For analysis of the infrared radiation emitted by stromata, a high-resolution infrared camera FLIR E50 was used. The visualization of stromata temperature profiles was shown in the form of pseudo-colored (false) infrared images. The 13C discrimination was used to characterize photosynthesis of the plant tissue enclosed within the stromata. The stromata had a substantially lower temperature than the green plant tissues. The difference reached ~5.6°C during midday hours, whereas it was smaller in the evening, reaching only ~3.6°C. The mycelium of Epichloë cultivated on agar showed about 2°C lower temperature in comparison to the surrounding. The plant tissues enclosed within the stroma were photosynthetically active, although this activity was of phosphoenolpyruvate carboxylase (PEPC) type and less involved in heat dissipation during the day. The stromata, built by fungal hyphae, on which fungal reproductive structures develop, form a cool shelter. This shelter provides a place for the larvae of Botanophila flies.


A case of metastatic adenocarcinoma on a background of penoscrotal extramammary Paget's disease.
A 77-year-old man presented with a chronic lesion located in the left penoscrotal area. Apart from pruritus, bleeding and an occasional discharge from this area, he also reported reduced appetite and weight loss. Examination revealed an ulcerated skin lesion attached to a firm subcutaneous mass. Wide local excision of the lesion revealed invasive adenocarcinoma on a background of extramammary Paget's disease. Staging studies showed disseminated metastatic disease within the lymph nodes, and liver and bone metastases. He was treated with carboplatin and paclitaxel chemotherapy initially, but then continued only on Carboplatin chemotherapy due to side effects from Paclitaxel. Eleven weeks after the start of his chemotherapy, his restaging imaging showed reduced lymphadenopathy, unchanged liver metastasis and sclerosis of bone metastasis. With completion of chemotherapy, repeat imaging showed stable disease. The patient is currently on follow-up.


Evaluating Hyperspectral Vegetation Indices for Leaf Area Index Estimation of Oryza sativa L. at Diverse Phenological Stages.
Hyperspectral reflectance derived vegetation indices (VIs) are used for non-destructive leaf area index (LAI) monitoring for precise and efficient N nutrition management. This study tested the hypothesis that there is potential for using various hyperspectral VIs for estimating LAI at different growth stages of rice under varying N rates. Hyperspectral reflectance and crop canopy LAI measurements were carried out over 2 years (2015 and 2016) in Meichuan, Hubei, China. Different N fertilization, 0, 45, 82, 127, 165, 210, 247, and 292 kg ha-1, were applied to generate various scales of VIs and LAI values. Regression models were used to perform quantitative analyses between spectral VIs and LAI measured under different phenological stages. In addition, the coefficient of determination and RMSE were employed to evaluate these models. Among the nine VIs, the ratio vegetation index, normalized difference vegetation index (NDVI), modified soil-adjusted vegetation index (MSAVI), modified triangular vegetation index (MTVI2) and exhibited strong and significant relationships with the LAI estimation at different phenological stages. The enhanced vegetation index performed moderately. However, the green normalized vegetation index and blue normalized vegetation index confirmed that there is potential for crop LAI estimation at early phenological stages; the soil-adjusted vegetation index and optimized soil-adjusted vegetation index were more related to the soil optical properties, which were predicted to be the least accurate for LAI estimation. The noise equivalent accounted for the sensitivity of the VIs and MSAVI, MTVI2, and NDVI for the LAI estimation at phenological stages. The results note that LAI at different crop phenological stages has a significant influence on the potential of hyperspectral derived VIs under different N management practices.


Galactose and cataract.
Galactosemia is a disorder caused by a deficiency of any one of three possible enzymes involved in the metabolism of galactose: galactokinase, transferase or epimerase. Any single deficient enzyme can result in cataract through the accumulation of galactitol in the lens. The ophthalmologist may play an important role in this disease, since early recognition of cataract development followed by the initiation of a galactose-free diet may lead to clearing of lenticular opacities. The clinical and laboratory findings that distinguish the three enzyme deficiency disorders of galactosemia are discussed. The biochemical genetics of each enzyme also are reviewed, along with the recent evidence linking heterozygous galactokinase deficiency and presenile cataract.


[Treatment modalities of nasopharyngeal angiofibroma].
Nasopharyngeal angiofibroma is a rare, benign vascular tumor originating from the sphenopalatine foramen. It primarily affects adolescent males. Due to its propensity to locally destructive growth, the tumor may lead to fatal epistaxis, intracranial extension, and life-threatening complications such as intraoperative hemorrhage. Many treatment modalities have been used for the management of nasopharyngeal angiofibroma, but surgery and external beam radiation therapy have proved to be the only effective treatment modalities with acceptable morbidity. While endoscopic surgery provides successful results for early stage tumors, recent technological advances in radiotherapy offer significant advantages in advanced and recurrent tumors.


A comparison of microleakages of five different recent bonding agents/systems in enamel and dentine.
This study compared the microleakages in enamel and dentine of newly developed bonding systems from different manufacturers. Fifteen or more extracted non-carious human premolars were used for each dental material system. The bonding systems were used with their respective composites. Cylindrical cavities were prepared in enamel (scored as a separate entity 0-3) and cementum/dentine (scored 0-4) on the buccal surface at the cemento-enamel junction and restored. The specimens were thermocycled, cut into slices and the depth of dye penetration scored. For enamel, the microleakage values of Clearfil Protect Bond (CPB; median = 1.0) and Xeno III (2.3) did not differ statistically (p > 0.05, Chi-square test), while the microleakage of CPB (1.0) was significantly better than that of GC Unifil Bond (GC; 3.0), Prime & Bond XP (P & B; 3.0) and Adper Prompt L-Pop (APL; 3.0), p < 0.05. At the cementum/dentine side significantly (p < 0.05) more microleakage for CPB (2.0) was found than for GC (0.0), P&B (0.5), APL (0.5), and Xeno III (0.5). Enamel was most effectively sealed by CPB and cementum/dentine by GC, P&B, APL and Xeno III. The chemical composition perse did not seem to determine the amount and location of microleakage.


Resistance of exotoxin A to purified Pseudomonas proteolytic enzymes.
Pseudomonas toxin is produced as a proenzyme which is cytotoxic for cells in culture but must be activated to express full enzymatic activity. The ability of purified pseudomonas alkaline protease and elastase or of culture filtrates of two strains of Pseudomonas aeruginosa to modify the activity of pseudomonas toxin was examined. Two parameters of toxin activity were followed: enzymatic activity, i.e., the adenosine diphosphate (ADP) ribosylation of elongation factor 2, and biological activity, i.e., inhibition of protein synthesis in cultured mouse fibroblasts. Biological activity of toxin depends upon an intact toxin molecule, whereas enzyme activity requires only a functional A region. Incubation with purified pseudomonas proteolytic enzymes did not alter either enzymatic or biological activity. The toxin is not refractory to the action of all proteolytic enzymes, since thermolysin rapidly destroyed the toxin molecule. Treatment of toxin with culture filtrates of P. aeruginosa reduced ADP ribosylation activity, but increased the ability of toxin to inhibit protein synthesis in cell monolayers. Incubation of culture filtrates with one of the protease inhibitors alpha-2-macroglobulin or phosphoramidon did not alter the effect of the filtrates on biological activity. Alpha-2-macroglobulin, however, caused a fourfold stimulation of ADP ribosylation activity of the toxin. We conclude that pseudomonas alkaline protease and elastase are not responsible for the modifications in toxin activity induced by culture filtrates of P. aeruginosa; the factors responsible have not yet been identified, but are not inactivated by phosphoramidon or alpha-2-macroglobulin.


Preoperative and intraoperative factors contributing to patient satisfaction after bi-cruciate stabilized total knee arthroplasty.
One of the causes of dissatisfaction following total knee arthroplasty (TKA) is abnormal knee kinematics. A newly designed bi-cruciate stabilized (BCS) TKA system has been developed to produce close-to-normal kinematics because of its anatomic tibiofemoral articular geometry and cam-post mechanism. Although BCS TKA is expected to improve patient satisfaction, no reports have described the appropriate technique or soft tissue handling required to achieve excellent satisfaction with BCS TKA. This study is to identify preoperative and intraoperative predictors of patient satisfaction after BCS TKA. Altogether, we studied 113 knees with primary varus knee osteoarthritis that underwent BCS TKA with a navigation system. Preoperative parameters including Knee Society Score and patient-reported scores [the Knee injury and Osteoarthritis Outcome Score (KOOS)] and intraoperative parameters including coronal, sagittal and axial alignment and joint laxity in each compartment that affected patient satisfaction was evaluated. Satisfaction score was evaluated with use of the 2011 Knee Society Scoring system. The multivariate regression analysis included age and preoperative and intraoperative parameters that correlated with satisfaction scores in the univariate analysis (P < 0.05). The mean satisfaction score was 28.2 ± 6.1. Multivariate regression analysis showed that the predictors of patient satisfaction were a preoperative high KOOS score for activities of daily living (P < 0.001), male sex (P = 0.005), older age (P = 0.027), and minimal medial joint laxity during flexion (P = 0.031). When performing BCS TKA, surgeons should pay attention to maintaining proper stability of the medial compartment, especially during flexion.


Null mutation of gp91phox reduces muscle membrane lysis during muscle inflammation in mice.
Muscle inflammation is a common feature in muscle injury and disease. Recently, investigators have speculated that inflammatory cells may increase or decrease muscle damage following modified muscle use, although there are few experimental observations to confirm either possibility. In the present study, a null mutation of gp91phox in neutrophils prevented superoxide production in cytotoxicity assays in which muscle cells were targets, and prevented most neutrophil-mediated cytolysis of muscle cells in comparison to wild-type neutrophils in vitro. We further tested whether deficiency in superoxide production caused a decrease in muscle membrane damage in vivo during modified muscle use. Gp91phox null mutant mice and wild-type mice were subjected to 10 days of muscle hindlimb unloading followed by reloading through return to normal locomotion, which induced muscle membrane lesions and muscle inflammation. Membrane lesions were quantified by measuring the presence of extracellular marker dye in reloaded soleus muscle fibres. There was a 90 % reduction in the number of fibres showing extensive membrane injury in gp91phox null mice compared to controls. Mutation of gp91phox did not change the concentration of neutrophils or macrophages in the reloaded muscle. Furthermore, muscle fibre growth during the reloading period was unaffected by the reduction in membrane injury. Together, these findings show that neutrophils can induce muscle membrane lysis through superoxide-mediated events, and indicate that superoxide-mediated membrane damage in vivo is not required for myeloid cell chemotaxis or muscle growth during muscle reloading.


Evidence-based medical leadership development: a systematic review.
Health systems invest significant resources in leadership development for physicians and other health professionals. Competent leadership is considered vital for maintaining and improving quality and patient safety. We carried out this systematic review to synthesise new empirical evidence regarding medical leadership development programme factors which are associated with outcomes at the clinical and organisational levels. Using Ovid MEDLINE, we conducted a database search using both free text and Medical Subject Headings. We then conducted an extensive hand-search of references and of citations in known healthcare leadership development reviews. We applied the Medical Education Research Study Quality Indicator (MERSQI) and the Joanna Briggs Institute (JBI) Critical Appraisal Tool to determine study reliability, and synthesised results using a meta-aggregation approach. 117 studies were included in this systematic review. 28 studies met criteria for higher reliability studies. The median critical appraisal score according to the MERSQI was 8.5/18 and the median critical appraisal score according to the JBI was 3/10. There were recurring causes of low study quality scores related to study design, data analysis and reporting. There was considerable heterogeneity in intervention design and evaluation design. Programmes with internal or mixed faculty were significantly more likely to report organisational outcomes than programmes with external faculty only (p=0.049). Project work and mentoring increased the likelihood of organisational outcomes. No leadership development content area was particularly associated with organisational outcomes. In leadership development programmes in healthcare, external faculty should be used to supplement in-house faculty and not be a replacement for in-house expertise. To facilitate organisational outcomes, interventions should include project work and mentoring. Educational methods appear to be more important for organisational outcomes than specific curriculum content. Improving evaluation design will allow educators and evaluators to more effectively understand factors which are reliably associated with organisational outcomes of leadership development.


Analysis of crypt cell proliferation in coeliac disease using MI-B1 antibody shows an increase in growth fraction.
This study aimed to investigate the pattern of cellular proliferation and to calculate the growth fraction of small intestinal crypts in 24 patients--eight with untreated coeliac disease (CD), six with treated CD, and 10 controls with normal villous architecture. Duodenal biopsy specimens were stained with MI-B1 antibody using an immunoperoxidase method. Positive stained crypt cells were counted and their position within each intact crypt column was noted. These were used to construct proliferation index distribution curves for each cell position from which the crypt growth fraction for each group of patients was calculated. The crypt growth fraction was found to be higher in the untreated CD group (0.57) than in the treated patients (0.39) and the controls (0.44). The mean (SEM) proliferative index for each crypt was significantly higher in the untreated group (42.3 (10.8)%; p < 0.05) than in the treated CD (21.7 (8.5)%) and control (19.7 (7.5)%) groups and correlated closely with the surface:volume index and enterocyte cell height measurements in all three groups. An increased growth fraction may contribute to other changes in crypt cell kinetics to produce the histological changes seen in untreated CD.


Can cerebellar and brainstem apparent diffusion coefficient (ADC) values predict neuromotor outcome in term neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia?
To determine the apparent diffusion coefficient (ADC) in specific infratentorial brain structures during the first week of life and its relation with neuromotor outcome for Hypoxic-ischemic encephalopathy (HIE) in term neonates with and without whole-body hypothermia (TH). We retrospectively evaluated 45 MRI studies performed in the first week of life of term neonates born between 2010 and 2013 at Boston Children's Hospital. Selected cases were classified into three groups: 1) HIE neonates who underwent TH, 2) HIE normothermics (TN), and 3) controls. The neuromotor outcome was categorized as normal, abnormal and death. The ADCmean was calculated for six infratentorial brain regions. A total of 45 infants were included: 28 HIE TH treated, 8 HIE TN, and 9 controls. The mean gestational age was 39 weeks; 57.8% were male; 11.1% were non-survivors. The median age at MRI was 3 days (interquartile range, 1-4 days). A statistically significant relationship was shown between motor outcome or death and the ADCmean in the vermis (P = 0.002), cerebellar left hemisphere (P = 0.002), midbrain (P = 0.009), pons (P = 0.014) and medulla (P = 0.005). In patients treated with TH, the ADC mean remained significantly lower than that in the controls only in the hemispheres (P = 0.01). In comparison with abnormal motor outcome, ADCmean was lowest in the left hemisphere (P = 0.003), vermis (P = 0.003), pons (P = 0.0036) and medulla (P = 0.008) in case of death. ADCmean values during the first week of life in the left hemisphere, vermis, pons and medulla are related to motor outcome or death in infants with HIE either with or without hypothermic therapy. Therefore, this objective tool can be assessed prospectively to determine if it can be used to establish prognosis in the first week of life, particularly in severe cases of HIE.


Anaphylactic histamine release from peritoneal mast cells of two inbred strains of rats sensitized with mouse IgE.
Peritoneal mast cells from rats of BH- and DA-inbred strains were compared for their capacity to passive sensitization in vitro with mouse IgE antibodies. In identical experimental conditions mast cells of BH-rats were good receptors for mouse IgE anti-KLH fraction and released histamine when challenged with specific antigen, whereas mast cells of DA-rats were much less sensitized and released little histamine on the challenge. In contrast, mast cells of DA-rats wee more susceptible to the challenge with anti-rat IgE and Concanavalin A, than were cells of BH-rats. This susceptibility correlated with total serum IgE level, which was higher in DA- than in BH-rats. These results show higher concentrations of IgE on mast cells of DA--rats. It is suggested that rat IgE present on normal mast cells may be one of the factors interfering in in vitro sensitization of the cells from DA-rats with mouse IgE antibodies.


Outcome of Anterior and Posterior Endoscopic Procedures for Cervical Radiculopathy Due to Degenerative Disk Disease: A Systematic Review and Meta-Analysis.
Systematic review and meta-analysis. Cervical spine endoscopic discectomy and decompression have gained popularity in the last decade. This review aimed to shed light on the current outcomes of cervical spine endoscopic procedures for degenerative disc disease (DDD) and to calculate a pooled estimate of various outcome measures. We retrieved articles published in English related to endoscopic cervical spine procedures from 3 central databases from inception until September 2020. A subgroup analysis based on the anterior versus the posterior approach was performed. Thirty-one articles fulfilled the eligibility criteria and included 1,410 patients. A successful outcome was observed in 91.3% (88.6-93.4%, P = 0.000). This percentage was lower for the anterior approach (89.6% [85.8-92.5%], P = 0.000) than for the posterior approach (94.2% [90.4-96.5%], P = 0.000). A higher percentage of poor outcomes was reported for the anterior approach (5.7% [3.2-10.1%], P = 0.000 vs. 2.3% [1-5.5%], P = 0.000 for the posterior approach). The overall complication rate was 7.2% (5.2-9.8%, P = 0.000). There was a slightly higher complication rate for the anterior approach (7.9% [4.5-13.3%], P = 0.000) than for the posterior approach (6.7% [4.4-10%], P = 0.000). The revision rate was 4.2% (2.6-6.8%, P = 0.000); and 4.2% (1.8-9.7%, P = 0.000) for the anterior approach and 4.00% (2.2-7.4%, P = 0.000) for the posterior approach. There is a higher success rate and lower complication rate with the posterior approach than with the anterior approach. However, high-quality randomized controlled trials are vital to evaluate the efficacy of these procedures.


Sequential KOtBu/FeCl3-catalyzed reductive phosphonylation of tertiary amides for the synthesis of α-amino phosphonates and phosphines.
A simple, mild and efficient sequential KOtBu/FeCl3-catalyzed reductive phosphonylation of tertiary amides is herein described. This process first involved the KOtBu-catalyzed selective semi-reduction of tertiary amides to hemiaminal intermediates by TMDS (1,1,3,3-tetramethyldisiloxane) and then the FeCl3-catalyzed nucleophilic addition of the hemiaminal intermediates to phosphonates, which allowed the straightforward synthesis of α-amino phosphonates in moderate to good yields. This method applied well to amides and lactams that bear no strong acidic α-hydrogens, and various functional groups, including methoxy, methylthio, cyano, halogen, and heterocycles, could be tolerated.


Curvilinear 3-D Imaging Using Row-Column-Addressed 2-D Arrays With a Diverging Lens: Feasibility Study.
Constructing a double-curved row-column-addressed (RCA) 2-D array or applying a diverging lens over the flat RCA 2-D array can extend the imaging field-of-view (FOV) to a curvilinear volume without increasing the aperture size, which is necessary for applications, such as abdominal and cardiac imaging. Extended FOV and low channel count of double-curved RCA 2-D arrays make 3-D imaging possible with equipment in the price range of conventional 2-D imaging. This paper proposes a delay-and-sum beamformation scheme specific to double-curved RCA 2-D arrays and validates its focusing ability based on simulations. A synthetic aperture imaging sequence with single element transmissions is designed for imaging down to 14 cm at a volume rate of 88 Hz. Using a diverging lens with an f-number of -1 circumscribing the underlying RCA array, the imaging quality of a double-curved λ/2 -pitch 3-MHz 62 + 62 RCA 2-D array is investigated as a function of depth within a curvilinear FOV of 60 °×60° . The simulated double-curved 2-D array exhibits the same full-width-at-half-maximum values for a point scatterer within its curvilinear FOV at a fixed radial distance compared with a flat 2-D array within its rectilinear FOV. The results of this paper demonstrate that the proposed beamforming approach is accurate for achieving correct time-of-flight calculations, and hence avoids geometrical distortions.


Clinical and Virological Characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) B.1.617.2 (Delta) Variant: A Prospective Cohort Study.
Data on the clinical and virological characteristics of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. This prospective cohort study compared the characteristics of the Delta variant to other variants. Adult patients with mild coronavirus disease 2019 (COVID-19) who agreed to daily saliva sampling at a community isolation facility in South Korea between July and August 2021 were enrolled. Scores of 28 COVID-19-related symptoms were recorded daily. The genomic RNA and subgenomic RNA from saliva samples were measured by real-time reverse-transcription polymerase chain reaction (PCR). Cell cultures were performed on saliva samples with positive genomic RNA results. A total of 141 patients (Delta group, n = 108 [77%]; non-Delta group, n = 33 [23%]) were enrolled. Myalgia was more common in the Delta group than in the non-Delta group (52% vs 27%, P = .03). Total symptom scores were significantly higher in the Delta group between days 3 and 10 after symptom onset. Initial genomic RNA titers were similar between the 2 groups; however, during the late course of disease, genomic RNA titers were higher in the Delta group. Negative conversion of subgenomic RNA was slower in the Delta group (median 9 vs 5 days; P < .001). The duration of viral shedding in terms of positive viral culture was also longer in the Delta group (median 5 vs 3 days; P = .002). COVID-19 patients infected with the Delta variant exhibited prolonged viable viral shedding with more severe symptoms than those infected with non-Delta variants.


Two-dimensional diffusion in the presence of topological disorder.
How topological defects affect the dynamics of particles hopping between lattice sites of a distorted, two-dimensional crystal is addressed. Perturbation theory and numerical simulations show that weak, short-ranged topological disorder leads to a finite reduction of the diffusion coefficient. Renormalization group theory and numerical simulations suggest that longer-ranged disorder, such as that from randomly placed dislocations or random disclinations with no net disclinicity, leads to subdiffusion at long times.


Attribute-based encryption scheme with multi-keyword search and supporting attribute revocation in cloud storage.
We propose an attribute-based encryption scheme with multi-keyword search and supporting attribute revocation in cloud storage environment, in which binary attributes and AND-gate access policy are used. Our proposal enjoys several advantages. Firstly, multi-keyword search is available, and only when a data user's attribute set satisfies access policy in keyword index, and keyword token generated by data user matches index successfully, then data user can obtain ciphertext containing keywords. In this way, more accurate keyword search is achievable. Secondly, the search privacy of data user is protected owing to cloud servers cannot obtain any knowledge of keywords which data user is interested in. Meanwhile, the ciphertext is able to be decrypted when data user's attribute set satisfies access policy specified in the ciphertext, which can both improve security of encryption and achieve secure fine-grained access control. Thirdly, the proposed scheme supports attribute revocation, in our scheme when a data user's attribute is revoked, the version number of attribute, non-revoked data users' secret keys and related ciphertexts will be updated, such that data user whose attribute is revoked does not decrypt updated ciphertext anymore. In addition, based on the assumption of decisional linear (DL) and decisional Diffie-Hellman (DDH), our scheme is proved to be secure against selectively chosen-keyword attacks and selectively chosen-plaintext attacks respectively, and it also ensures token privacy security.


Non-adherence to anti-hypertensive medications in a low-resource country Nepal: a systematic review and meta-analysis.
Nepal is a low resource country with cardiovascular diseases being the number one cause of mortality. Despite hypertension being the single most important risk factor for cardiovascular diseases, non-adherence to anti-hypertensive medications has not been assessed systematically. So, this systematic review and meta-analysis aims to analyze the prevalence of non-adherence to anti-hypertensive medications in Nepal. This systematic review and meta-analysis was piloted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Electronic databases of Embase, PubMed, Scopus, Web of Science, Cochrane Library, Cinhal Plus, and Google Scholar were searched from inception till 1 February 2023. The random-effects model with 95% confidence interval (CI) was used to calculate the non-adherence rate. Altogether, 14 studies with a total of 3276 hypertensive patients were included in the meta-analysis. The pooled prevalence of non-adherence to anti-hypertensive medications was 49% (95% CI: 0.37-0.62, I2=98.41%, P<0.001). The non-adherence rate using Morisky Medication Adherence Scale (MMAS) was 55% (95% CI: 0.34-0.76, I2=99.14%, P<0.001), and using Hill-Bone Compliance Scale, the non-adherence rate was 45% (95% CI: 0.37-0.54, I2=84.36%, P<0.001). In subgroup analysis, the non-adherence was higher in rural areas 56% (95% CI: 0.51-0.61, I2=0.0%, P=0.46) compared to urban areas 42% (95% CI: 0.31-0.54, I2=96.90%, P<0.001). The trend of non-adherence was increasing after 2020. Additionally, forgetfulness, carelessness, cost of medications, number of comorbidities, and using an alternate form of medication were common factors associated with non-adherence. This meta-analysis showed that half of the hypertensive population of Nepal are non-adherent to their anti-hypertensive medications, thereby posing a significant long-term cardiovascular consequence among Nepali population.


Surgical Treatment of Eosinophilic Cystitis in Adults: A Report of Two Cases and a Literature Review.
Eosinophilic cystitis is a rare disease that presents with either urinary frequency, hematuria, suprapubic pain or urinary retention. Although benign, this entity may progress to diffuse bladder involvement with the need for surgical treatment. We report on 2 cases of advanced disease that required cystectomy with very complex lower urinary tract reconstruction, and review the literature of surgically treated cases.


ELOVL4-Mediated Production of Very Long-Chain Ceramides Stabilizes Tight Junctions and Prevents Diabetes-Induced Retinal Vascular Permeability.
Tight junctions (TJs) involve close apposition of transmembrane proteins between cells. Although TJ proteins have been studied in detail, the role of lipids is largely unknown. We addressed the role of very long-chain (VLC ≥26) ceramides in TJs using diabetes-induced loss of the blood-retinal barrier as a model. VLC fatty acids that incorporate into VLC ceramides are produced by elongase elongation of very long-chain fatty acids protein 4 (ELOVL4). ELOVL4 is significantly reduced in the diabetic retina. Overexpression of ELOVL4 significantly decreased basal permeability, inhibited vascular endothelial growth factor (VEGF)- and interleukin-1β-induced permeability, and prevented VEGF-induced decrease in occludin expression and border staining of TJ proteins ZO-1 and claudin-5. Intravitreal delivery of AAV2-hELOVL4 reduced diabetes-induced increase in vascular permeability. Ultrastructure and lipidomic analysis revealed that ω-linked acyl-VLC ceramides colocalize with TJ complexes. Overall, normalization of retinal ELOVL4 expression could prevent blood-retinal barrier dysregulation in diabetic retinopathy through an increase in VLC ceramides and stabilization of TJs.


Breast lesion detection and characterization with 3D features.
Automated Breast Ultrasound (ABUS) is highly effective as breast cancer screening adjunct technology. Automation can greatly enhance the efficiency of the clinician sifting through the quantum of data in ABUS volumes to spot lesions. We have implemented a fully automatic generic algorithm pipeline for detection and characterization of lesions on such 3D volumes. We compare a wide range of features for region description on their effectiveness at the dual goals of lesion detection and characterization. On multiple feature images, we compute region descriptors at lesion candidate locations obviating the need for explicit lesion segmentation. We use Random Forests classifier to evaluate candidate region descriptors for lesion detection. Further, we categorize true lesions as Malignant or other masses (e.g. Cysts). Over a database of 145 volumes, with 36 biopsy verified lesions, we achieved Area Under the Curve (AUC) values of 92.6% for lesion detection and 89% for lesion characterization.


Functional knockdown of VCAM-1 at the posttranslational level with ER retained antibodies.
Vascular cell adhesion molecule 1 (VCAM-1) is involved in the recruitment of leukocytes to inflammatory sites. In this study we present the first functional knockdown of VCAM-1 using an ER retained antibody construct. We generated a knockdown construct encoding the VCAM-1 specific single chain variable fragment scFv6C7.1 fused to the C-terminal ER retention sequence KDEL. HEK-293:VCAM-YFP cells stably expressing a VCAM-YFP fusion protein were transiently transfected with the knockdown construct and showed down-regulation of surface VCAM-1. Knockdown efficiency of the system is time-dependent due to used transient transfection of the intrabody construct. Furthermore, intrabody mediated knockdown of HEK-293:VCAM-YFP cells also impaired cell-cell interaction with Jurkat cells that are endogenously expressing VLA-4, the physiological partner of VCAM-1. Posttranslational knockdown with ER retained antibodies seems to be a promising technique, as shown here for VCAM-1.


Antithrombotic effect of PMC, a potent alpha-tocopherol analogue on platelet plug formation in vivo.
Platelet thrombi formation was induced by irradiation of mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. PMC (2, 2, 5, 7, 8-pentamethyl-6-hydroxychromane; 20 microg/g, i.v.) significantly prolonged the latent period of inducing platelet plug formation in mesenteric venules. When fluorescein sodium was given at 10 microg/kg, PMC (20 microg/g) delayed occlusion time by about 1.7-fold. Furthermore, aspirin (250 microg/g) also showed similar activity in delaying the occlusion time. On a molar basis, PMC was about 14-fold more potent than aspirin at delaying the occlusion time. PMC was also effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice when administered intravenously at doses of 5 and 10 microg/g. In addition, intravenous injection of PMC (5 microg/g) significantly prolonged bleeding time by about 1.6-fold compared with normal saline in severed mesenteric arteries of rats. Continuous infusion of PMC (1 microg/g/min) significantly increased the bleeding time by about 1.6-fold and the bleeding time was also significantly prolonged for up to 90 min after cessation of PMC infusion. These results suggest that PMC has an effective antiplatelet effect in vivo and may be a potential therapeutic agent for arterial thrombosis, but must be assessed further for toxicity.


Different susceptibility to fatty liver-haemorrhagic syndrome in young and older layers and the interaction on blood LDL-C levels between oestradiols and high energy-low protein diets.
1. The objective of the study was to investigate the susceptibility of young and older laying hens to fatty liver-haemorrhagic syndrome (FLHS) and to evaluate the reliability of different blood lipid fractions for predicting or diagnosing FLHS. 2. Forty young hens and 40 older hens were caged individually. Each group of hens was randomly allotted to four treatments for 21 days: either a control, an oestradiol group, a high energy-low protein diet (HELPD) group or a HELPD + oestradiol group. Blood levels of oestradiol, triglyceride (TG), cholesterol (CHOL), high density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), liver total lipids, hepatic haemorrhagic scores and productive performance were assessed. 3. In older hens, β-oestradiol increased (P < 0.05) liver total lipids, hepatic haemorrhagic scores and the incidence of FLHS but reduced (P < 0.05) productive performance; however, such changes were not observed in young hens. 4. In two groups of hens, serum TG, CHOL and HDL-C levels were increased (P < 0.001) by β-oestradiol. Hens with FLHS had higher serum TG, CHOL and HDL-C (P < 0.001) than non-FLHS birds in the older layer group of hens. 5. An interaction (β-oestradiol × HELPD) (P < 0.05) for LDL-C levels was observed in both groups of hens. In young hens, β-oestradiol induced a decrease (P = 0.004) in serum LDL-C levels but the effect was attenuated by HELPD. In older hens, HELPD caused an increase (P = 0.02) in serum LDL-C although the effect depended on the presence of β-oestradiol. 6. In conclusion, older layers were more susceptible to FLHS than young layers after oestradiol treatment. Blood TG, CHOL and HDL-C rather than LDL-C levels can be used as a prediction tool for the overall susceptibility to FLHS in older rather than young layers. There were interactions between oestradiol and HELPD on blood LDL-C levels in laying hens.


Assessing the pulse rate in adult patients.
Assessing the pulse is a common procedure and an important aspect of many nursing interventions; it should always be done with care and reassessed as needed. Assessment should always be taken seriously, with any deviations from the norm reported to a senior clinician, and pulse rate, rhythm and strength must always be documented. Pulses indicate numerous patient characteristics including the degree of relaxation, regularity of cardiac contractions and sufficiency of cardiac output. This article considers the relevant anatomy, physiology and practice of pulse assessment and recording.


Selection Criteria for Cochlear Implantation in the United Kingdom and Flanders: Toward a Less Restrictive Standard.
The impact of the newly introduced cochlear implantation criteria of the United Kingdom and Flanders (Dutch speaking part of Belgium) was examined in the patient population of a tertiary referral center in the Netherlands. We compared the patients who would be included/excluded under the new versus old criteria in relation to the actual improvement in speech understanding after implantation in our center. We also performed a sensitivity analysis to examine the effectiveness of the different preoperative assessment approaches used in the United Kingdom and Flanders. The selection criteria were based on preoperative pure-tone audiometry at 0.5, 1, 2, and 4 kHz and a speech perception test (SPT) with and without best-aided hearing aids. Postoperatively, the same SPT was conducted to assess the benefit in speech understanding. The newly introduced criteria in Flanders and the United Kingdom were less restrictive, resulting in greater percentages of patients implanted with CI (increase of 30%), and sensitivity increase of 31%. The preoperative best-aided SPT, used by both countries, had the highest diagnostic ability to indicate a postoperative improvement of speech understanding. We observed that patient selection was previously dominated by the pure-tone audiometry criteria in both countries, whereas speech understanding became more important in their new criteria. Among patients excluded by the new criteria, seven of eight (the United Kingdom and Flanders) did exhibit improved postoperative speech understanding. The new selection criteria of the United Kingdom and Flanders led to increased numbers of postlingually deafened adults benefitting from CI. The new British and Flemish criteria depended on the best-aided SPT with the highest diagnostic ability. Notably, the new criteria still led to the rejection of candidates who would be expected to gain considerably in speech understanding after implantation.


Changes in the caldesmon isoform content and intimal thickening in the rabbit carotid artery induced by a silicone elastomer collar.
The presence of a silicone elastomer collar around one carotid artery of a rabbit induces thickening of the tunica intima. We used immunoblotting to study quantitatively changes in the isoforms of caldesmon, a protein implicated in the regulation of contractility in smooth muscle, while also monitoring the histological changes during 28 days after collaring. Control rabbit carotid arteries (n = 28) contained 245 +/- 6.4 nmol/g protein of the larger isoform of caldesmon (CDh) and 68.3 +/- 3.6 nmol/g protein of the smaller isoform (CD1). Four days after collaring, intimal thickening was slight, but 44% of arterial CDh had been lost; this loss of CDh was therefore from the tunica media. At 10 days, CDh fell to 37% of the control level. Immunofluorescence using CDh-specific antibodies showed that the CDh level was diminished but remained uniform across the wall of collared arteries. At 14 days, when intimal thickening was maximal, there was 30% more CD1 than in controls. At 28 days, the neointima had thinned, and CD1 had fallen to below control levels. Thus, CD1 levels reflected the development and regression of neointima. Changes in caldesmon isoforms showed that smooth muscle cell phenotypic changes occurred throughout the arterial wall.


[Uncertain analgetic efficacy of intraurethral instillation of anesthetic jelly in rigid cystoscopy for men].
The analgetic efficacy of intraurethral instillation of anesthetic jelly in rigid cystoscopic examination for men is not clearly confirmed. This study evaluated the usefulness of intraurethral instillation of anesthetic jelly by questionnaires regarding the pain and uncomfortable feelings during and after the cystoscopic examination. A total of 62 men were enrolled in the study. Sixteen patients had not received cystoscopy previously (first cases), and 46 had prior experiences of cystoscopy more than twice (repeat cases). These patients were sequentially divided into two groups; one group (jelly-group) received intraurethral instillation of oxybuprocaine hydrochroride jelly (Benoxil jelly) prior to cystoscopic examination, and the other group (no-jelly-group) did not receive the jelly instillation. Pain during the jelly instillation to examination, and uncomfortable feelings at micturition after the examination was evaluated by questionnaires. Instillation of the jelly itself caused considerable pain, which almost similar to that of scope insertion. There was no significant difference in pain score between jelly-group and no-jelly-group during the insertion of the scope to examination. The miction pain after examination was significantly severer in the jelly-group than in the no-jelly-group in repeat cases. In addition, 75% of repeat cases felt better comfortableness when jelly was not instilled, and 96% of repeat cases did not want jelly instillation for their future examination. Intraurethral instillation of anesthetic jelly had no efficacy for reducing the pain during cystoscopy. Instillation of the jelly itself caused considerable pain, and it made pain and uncomfortable feelings after the examination worse. These results suggested that the instillation of anesthetic jelly before rigid cystoscopy in men might not be useful enough for reducing the uncomfortable feeling during the examination.


Our wealth, our health--bellwether industries for decision tools and symbiotic stewardships.
This chapter examines the tea leaves of emerging technologies for the most fruitful areas of crossover value to health decisions, by spotting bellwether industries of similar information asymmetries. It examines changing tools and roles for growing consumer-centrism in personal finance, healthcare, private aviation, and law. It seeks to understand the technologies of managing and measuring, the transformations of growing transparencies in our processes, and how an increasing sense of collective stewardship forged between people and their machines can lead beyond effectiveness to wisdom, for individuals, communities, and the world. "The whole thing reminds me of the uncomfortable feeling I experienced when I first sought out investment advice. . . ..I concluded that I had to undertake the generalist's job myself; I had to take the high-level management of my investments into my own hands. Similarly, given the structure of the medical practice associated with prostate cancer, that's the only viable choice any patient has." Andy Grove, Co-Founder and Chair, Intel. "In the end, a symbiotic culture composed of human and digital individuals may be a more effective steward of the earth's resources than humans would be by themselves." Donald D. Chamberlin, author and ACM Fellow.


Perception of quality of health delivery and health insurance subscription in Ghana.
National health insurance schemes (NHIS) in developing countries and perhaps in developed countries as well is a considered a pro-poor intervention by helping to bridge the financial burden of access to quality health care. Perceptions of quality of health service could have immense impacts on enrolment. This paper shows how perception of service quality under Ghana's insurance programme contributes to health insurance subscription. The study used the 2014 Ghana Demographic and Health Survey (GDHS) dataset. Both descriptive proportions and binary logistic regression techniques were applied to generate results that informed the discussion. Our results show that a high proportion of females (33 %) and males (35 %) felt that the quality of health provided to holders of the NHIS card was worse. As a result, approximately 30 % of females and 22%who perceived health care as worse by holding an insurance card did not own an insurance policy. While perceptions of differences in quality among females were significantly different (AOR = 0.453 [95 % CI = 0.375, 0.555], among males, the differences in perceptions of quality of health services under the NHIS were independent in the multivariable analysis. Beyond perceptions of quality, being resident in the Upper West region was an important predictor of health insurance ownership for both males and females. For such a social and pro-poor intervention, investing in quality of services to subscribers, especially women who experience enormous health risks in the reproductive period can offer important gains to sustaining the scheme as well as offering affordable health services.


Dental caries in rural and urban black preschoolchildren.
The dentitions of 439 rural and 192 urban black children aged 1-5 years were examined with mirror and probe. Dental caries was common and the percentage prevalence and dmft values were similar in children of 1-3 years in both groups. At 4 years of age there was a twofold increase in dental caries in the urban children to reach a dmft score significantly greater than that in the rural children (P less than 0.01). Labial caries was common in rural children but rare in urban children while rampant caries (dmft greater than or equal to 5) exhibited the opposite pattern.


Management of pregnant and postnatal women with pre-existing diabetes or cardiac disease using multi-disciplinary team models of care: a systematic review.
More women with an increased risk of poor pregnancy outcome due to pre-existing medical conditions are becoming pregnant. Although clinical care provided through multi-disciplinary team (MDT) working is recommended, little is known about the structure or working practices of different MDT models, their impact on maternal and infant outcomes or healthcare resources. The objectives of this review were to consider relevant international evidence to determine the most appropriate MDT models of care to manage complex medical conditions during and after pregnancy, with a specific focus on pre-existing diabetes or cardiac disease in high income country settings. Quantitative and qualitative evidence of MDT models of care for the management of pregnant/postnatal women with pre-existing diabetes and cardiac disease was considered. A search of the literature published between January 2002 - January 2014 was undertaken. Methodological quality was assessed using checklists developed by the Joanna Briggs Institute. Given limited primary and secondary research evidence, guidelines and opinion papers were included. Two independent reviewers conducted critical appraisal of included papers. Nineteen papers were included from UK, Canada, USA, the Netherlands and Singapore. No studies were found which had compared MDT models for pregnant/postnatal women with pre-existing diabetes or cardiac disease. Two small retrospective studies reported better outcomes for women with cardiac disease if an MDT approach was used, although evidence to support this was limited. Due to study heterogeneity it was not possible to meta-analyse data. No evidence was identified of MDT management in the postnatal period or impacts of MDT working on healthcare resources. Despite widespread promotion of MDT models of care for pregnant and postnatal women with pre-existing diabetes or cardiac disease, there is a dearth of primary evidence to inform structure or working practices or beneficial impact on maternal and infant outcomes or healthcare resources. Primary research into if or how MDT models of care improve outcomes for women with complex pregnancies is urgently needed.


The assessment of a structured online formative assessment program: a randomised controlled trial.
Online formative assessment continues to be an important area of research and methods which actively engage the learner and provide useful learning outcomes are of particular interest. This study reports on the outcomes of a two year study of medical students using formative assessment tools. The study was conducted over two consecutive years using two different strategies for engaging students. The Year 1 strategy involved voluntary use of the formative assessment tool by 129 students. In Year 2, a second cohort of 130 students was encouraged to complete the formative assessment by incorporating summative assessment elements into it. Outcomes from pre and post testing students around the formative assessment intervention were used as measures of learning. To compare improvement scores between the two years a two-way Analysis of Variance (ANOVA) model was fitted to the data. The ANOVA model showed that there was a significant difference in improvement scores between students in the two years (mean improvement percentage 19% vs. 38.5%, p < 0.0001). Students were more likely to complete formative assessment items if they had a summative component. In Year 2, the time spent using the formative assessment tool had no impact on student improvement, nor did the number of assessment items completed. The online medium is a valuable learning resource, capable of providing timely formative feedback and stimulating student-centered learning. However the production of quality content is a time-consuming task and careful consideration must be given to the strategies employed to ensure its efficacy. Course designers should consider the potential positive impact summative components to formative assessment may have on student engagement and outcomes.


Novel jasmonate amino acid conjugates in Asparagus officinalis during harvest-induced and natural foliar senescence.
Five jasmonates, including novel tryptophan conjugates of jasmonic acid and dihydrojasmonic acid, were identified in extracts from spears of Asparagus officinalis L. by electrospray tandem mass spectrometry. Spears were harvested and were held dry or with bases immersed in water. The concentrations of jasmonic acid, dihydrojasmonic acid, their tryptophan conjugates, cucurbic acid and methyl jasmonate, were measured by ELISA in spears in the 10 d following harvest. A transient increase that occurred in all spear tips immediately following harvest in the concentration of jasmonates can be attributed to a wounding response. A second increase in the concentration of jasmonates occurred from 7 d after harvest but only in dry-treated spear tips indicating that jasmonates may have accumulated in response to water stress. Jasmonate levels were also monitored during natural foliar senescence. Increased levels of jasmonates occurred after the onset of senescence, implicating them as a consequence rather than a cause of senescence.


A review of Intra-uterine foetal deaths at the Cape Coast Teaching Hospital.
To estimate the rate of IUFD/Stillbirths (SB). This is a retrospective review of delivery suite records from Jan 1 2013 to Dec 31 2014. Study was undertaken at the Cape Coast Teaching Hospital (CCTH) in the Central region of Ghana. All pregnant women who had their babies at the delivery suite of CCTH have their records hand written in Ghana health service approved and distributed delivery records book. We identified all patients with IUFD/SB from this delivery suite record book which is kept on the delivery suite. The data collected included the age, parity, mode of delivery, total blood loss, sex of the foetus and condition of foetus i.e. Macerated stillbirth (MSB) or fresh still birth (FSB). Of the 315 IUFDs found in the records book, 26 were incompletely filled, and 13 were abortions (<28 weeks) and therefore excluded. The analysis is therefore based on 276 completed documentations. The data collected from the delivery suite records were analysed using STATA version 11.0. Of the 315 IUFD/SBs documented in the delivery suite record book, 13 were abortions (<28 weeks), leaving 302 IUFD/SBs. Of this number, 26 had incomplete data and were excluded from the analysis. The analysis was thus based on 276 IUFD/SBs with complete data. Over the study period there were 5176 deliveries, giving a stillbirth rate of 58.5/1000 deliveries. Majority of the IUFD occurred in women 20-35 years of age (74.7%), and who have had two or less births (66.7%). The mean maternal age at which IUFD occurred was 29 years. Our review shows that the SBR of 58.5/1000, over the two years, at CCTH is high. We suggest further studies to focus on the reasons for IUFDs and what interventions can be applied to reduce it. No internal or external funds sourced.


Drill down with root cause analysis.
Review the structure of an effective critical event analysis and suggestions for completing documentation and maximizing knowledge while protecting your organization from litigation.


Nrf2 mediates the protective effects of homocysteine by increasing the levels of GSH content in HepG2 cells.
Homocysteine (Hcy) and glutathione (GSH) are crucial reduction‑oxidation mediators. The underlying mechanisms governing the effects of Hcy on GSH generation in the progression of alcoholic liver disease has so far received little attention. The present study hypothesized that the antioxidant transcriptional factor nuclear factor (erythroid‑derived 2)‑like 2 (Nrf2) may participate in Hcy‑mediated regulation of GSH production in HepG2 human liver cancer cells. MTT assay was used to study the cytotoxicity of homocysteine, western blot analysis and immunofluorescence staining were used to determine the effect of Hcy on Nrf2 expression. Our data demonstrated that HepG2 cells exposed to exogenous levels of Hcy (0‑100 µM) exhibited elevated GSH levels in a concentration‑dependent manner. Furthermore, 4‑hydroxynonenal (4‑HNE)‑induced cell injury was attenuated by Hcy; however, this protective effect was blocked by the GSH‑production inhibitor buthionine sulfoximine. Hcy treatment was able to induce Nrf2 protein expression in HepG2 cells. Treatment with the Nrf2 activator tert‑butylhydroquinone (0‑100 µM) increased GSH expression in a concentration‑dependent manner; however, Nrf2‑siRNA abolished the Hcy‑induced increase in GSH expression and cellular protection in 4‑HNE‑stressed HepG2 cells. In conclusion, the antioxidant transcriptional factor Nrf2 was demonstrated to mediate the Hcy‑induced increase in GSH expression levels and cellular protection in HepG2 cells.